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Nerve growth factor treatment in dementia.

Millions of people are affected by Alzheimer disease. As longevity increases, so will the number of patients with dementia. This has led to an intense search for successful treatment strategies. One area of interest is neurotrophic factors. Brain development and neuronal maintenance, as well as protective efforts, are mediated by a large number of different neurotrophic factors acting on specific receptors. In neurodegenerative disorders, there may be a possibility of rescuing degenerating neurons and stimulating terminal outgrowth with use of neurotrophic factors. The first neurotrophic factor discovered was nerve growth factor (NGF). A wealth of animal studies have shown that cholinergic neurons are NGF sensitive and NGF dependent, which is especially interesting in cognitive disorders, in which central cholinergic projections are important for cognitive function. In Alzheimer disease, cholinergic neurons have been shown to degenerate. This suggests that NGF may be used to pharmacologically counteract cholinergic degeneration and/or induce terminal sprouting in Alzheimer disease. Data from animal studies, as well as from the author's recent clinical trial, in which NGF was infused to the lateral ventricle in patients with Alzheimer disease, will be presented. Effects of NGF on cognition, as well as issues regarding dosage, side effects, and alternative ways of administering NGF, will be discussed.

Alzheimer Disease↗

Successful treatment of erythromelalgia with intrathecal hydromorphone and clonidine.

OBJECTIVE: The objective of this study was to determine if intractable pain from erythromelalgia could be successfully treated with intrathecal hydromorphone and clonidine. DESIGN: A single case of pain from erythromelalgia refractory to multiple treatment modalities was examined and treated. SETTING: The setting is an outpatient pain clinic at a major university teaching hospital. PATIENT: Our patient is an 82-year-old woman with hypertension and peripheral vascular disease. INTERVENTION: Intrathecal opioid and an alpha2-agonist were administered. OUTCOME MEASURES: Outcome was determined by means of patient self-report during office follow-up visits. RESULTS AND CONCLUSIONS: Administration of intrathecal opioid and an alpha2-agonist can be effective in the treatment of the pain of erythromelalgia and offers an alternative pain treatment modality for patients with unremitting pain refractory to more conservative therapy.

Adrenergic alpha-Agonists↗

Continuous intrathecal baclofen infusion for symptomatic generalized dystonia.

Five patients with generalized dystonia who were refractory to oral medications were treated by continuous intrathecal baclofen infusion. Dystonia was related to cerebral palsy in three patients and to Hallervorden-Spatz disease in two. Responsiveness to intrathecally administered baclofen was evaluated after bolus injections in one patient and during continuous infusions via an external micropump in four. Patients who responded to trial injections were subsequently implanted with a programmable pump for continuous infusion of baclofen. Dystonia in the three patients were cerebral palsy was substantially improved by continuous intrathecal baclofen infusion in doses of 500 to 800 micrograms/d. Benefit has persisted for > 19 months of continuous infusion. Dystonia in the two patients with Hallervorden-Spatz disease was not improved, although the screening trial was limited by side effects in one patient and by meningitis in the other. We conclude that continuous intrathecal baclofen infusion is beneficial therapy for some patients with generalized dystonia and that additional investigations are indicated.

Adolescent↗

Subfascial implantation of intrathecal baclofen pumps in children: technical note.

OBJECTIVE: Indwelling intrathecal drug delivery systems are becoming increasingly important as a method of neuromodulation within the nervous system. In particular, intrathecal baclofen therapy has shown efficacy and safety in the management of spasticity and dystonia in children. The most common complications leading to explantation of the pumps are skin breakdown and infection at the pump implantation site. The pediatric population poses particular challenges with regard to these complications because appropriate candidates for intrathecal baclofen therapy are often undernourished and thus have a dearth of soft tissue mass to cover a subcutaneously implanted baclofen pump. We report a technique of subfascial implantation that provides greater soft tissue coverage of the pump, thereby reducing the potential for skin breakdown and improving the cosmetic appearance of the implantation site. METHODS: Eighteen consecutively treated children (average age, 8 yr, 7 mo) with spasticity and/or dystonia underwent subfascial implantation of a baclofen pump. These children's mean weight of 42.9 lb is less than the expected weight for a group of children in this age group, ranging from 4 years, 8 months, to 15 years, 7 months. In all patients, the pump was inserted into a pocket surgically constructed between the rectus abdominus and the external oblique muscles and the respective anterior fascial layers. RESULTS: At an average follow-up of 13.7 months, no infection or skin breakdown had occurred at the pump surgical site in any of the 18 patients. CONCLUSION: At this early follow-up, the subfascial implantation technique was associated with a reduced rate of local wound and pump infections and provided optimal cosmetic results as compared with that observed in retrospective cases.

Adolescent↗

Reversible urinary retention secondary to excessive morphine delivered by an intrathecal morphine pump.

Reversible complication of intrathecal morphine delivered by an implanted pump is described in one patient. The patient was evaluated initially using a contrast CT of the thoracic spine as well as urodynamics studies. After decreasing the intrathecally administered morphine from 2 mg/24 hr to .5 mg/24 hr, the patient's neurogenic bladder reversed within 4 days. Implanted pumps to deliver intrathecal narcotic medications are being used currently to treat intractable pain. This is a case report of reversible urinary retention secondary to the intrathecal narcotic.

Aged↗

Scintigraphic evaluation of intrathecal infusion systems: selection of patients for surgical or medical management.

PURPOSE: Continuous intrathecal medication through a surgically implanted infusion system is an established method for treating intractable spasticity or pain. To determine if imaging can guide surgical or medical management in patients with suspected infusion system malfunction, we reviewed our experience in evaluating the functional status of these systems with indium-111 DTPA scintigraphy. METHODS: We retrospectively reviewed 23 indium-111 DTPA studies in 19 patients (7 female, 12 male; ages 20-83 years, average age 47 years). Indications included intractable spasticity or increasing pain. Infusion systems were classified scintigraphically as either functioning or malfunctioning; malfunctions were further classified as either mechanical or catheter-related. Imaging findings were correlated with subsequent clinical management. RESULTS: Fifteen of 23 (65%) studies demonstrated functioning infusion systems; these patients were all treated medically. Eight of 23 (35%) studies demonstrated malfunctioning systems; 6 of 8 were subsequently treated surgically and 2 of 8 medically. CONCLUSION: Indium-111 DTPA scintigraphy can differentiate between functioning and malfunctioning infusion systems, guiding appropriate medical or surgical management.

Adult↗

Intrathecal baclofen for spasticity of cerebral palsy: project coordination and nursing care.

Spasticity caused by cerebral palsy is painful and disabling. Infusion of an intrathecal antispasmodic for relief is investigated in a multicenter, interdisciplinary clinical trial. Clinical nurse specialists coordinate local team endeavors. The nursing process serves as a functional framework for project development, protocol implementation and long-term patient follow-up.

Adolescent↗

Epidural analgesia in a patient with an intrathecal catheter and subcutaneous pump to deliver baclofen.

Baclofen is used for the treatment of spasticity. Small doses administered intrathecally achieve high cerebrospinal fluid concentrations with reduced side-effects. Pediatric anesthesiologists are often reluctant to consider epidural analgesia in children receiving baclofen via an intrathecal catheter and subcutaneous pump. This reluctance is based on concerns for damaging the intrathecal catheter and introducing infection. In addition, the acute cessation of intrathecal baclofen can precipitate a life-threatening withdrawal state. We report a case of successful epidural analgesia in a patient receiving intrathecal baclofen and discuss the steps we took to minimize the chance of harm with this technique. We conclude that an intrathecal catheter and subcutaneous pump to deliver baclofen should not preclude the use of an epidural catheter for perioperative analgesia.

Adolescent↗

Intrathecal drug delivery for treatment of chronic low back pain: report from the National Outcomes Registry for Low Back Pain.

OBJECTIVE: To obtain data on patient demographics, clinical practices, and long-term outcomes for patients with chronic low back pain treated with implantable drug-delivery systems. DESIGN: The National Outcomes Registry for Low Back Pain collected data at baseline, trialing, implant (or decision not to implant), and at 6- and 12-month follow-ups. Data were collected at all time points, regardless of implant status. OUTCOME MEASURES: Numeric pain ratings and Oswestry Low Back Pain Disability scores from implanted patients were compared among baseline and 6- and 12-month follow-ups. Patients were also asked to rate their quality of life and satisfaction with the therapy. RESULTS: Thirty-six physicians enrolled 166 patients to be trialed for drug-delivery systems. The trialing success rate was 93% (154 patients). In all, 136 patients (82%) were implanted. In the implant group, numeric pain ratings dropped by more than 47% for back pain and more than 31% for leg pain at the 12-month follow-up. More than 65% of implanted patients reduced their Oswestry scores by at least one level at their 12-month follow-ups compared with baseline. At 12-month follow-ups, 80% of implanted patients were satisfied with their therapy and 87% said they would undergo the procedure again. CONCLUSIONS: Current clinical practices related to trialing of drug-delivery systems resulted in the majority of patients successfully trialed. At 12-month follow-ups, implanted patients experienced reductions in numeric back and leg pain ratings, improved Oswestry scores, and high satisfaction with the therapy.

Adult↗

Efficacy of intrathecal bupivacaine: how important is the flow rate?

We present two cases of cancer patients with intractable mechanical and visceral pain that was unrelieved with either comprehensive medical management or intrathecal morphine who received intrathecal bupivacaine. While the continuous administration of a seemingly significant daily dose neither relieved pain nor caused measurable clinical changes, the addition of small, presumably negligible bolus doses on top of the continuous infusion resulted in spectacular pain control, clear thermoanalgesic suspended block, and in one of the patients, significant hypotension. To the best of our knowledge, such an observation has neither been reported before nor can we provide a satisfactory explanation for it. However, we believe it may have significant implications for the treatment of some patients, in particular, cancer patients with mechanical pain that cannot be adequately relieved with morphine whatever the route of administration.

Aged↗

Intrathecal hydromorphone for intractable nonmalignant pain: a retrospective study.

BACKGROUND: Hydromorphone is often administered intrathecally for the treatment of cancer and nonmalignant chronic intractable pain. It is frequently utilized in combination with other analgesics in a multidrug intrathecal infusion; however, very little data are available documenting efficacy or safety of intrathecal hydromorphone as a solo analgesic. OBJECTIVE: This study was conducted to examine pain and side effects in patients receiving intrathecal hydromorphone. DESIGN: A retrospective review was conducted of all patients receiving intrathecal hydromorphone monotherapy in two large pain specialty practices in the Pacific Northwest. All data collected within 30 days of the patient's 3-month, 6-month, and 12-month anniversary of implant were analyzed. PATIENTS: Twenty-four patients with noncancer-related chronic pain were included in the study. Thirteen patients had eligible pain data at 1 month, 10 patients had pain data at 3 months and seven patients had pain data available at 12 months after initiation of intrathecal hydromorphone. RESULTS: Average pain scores decreased significantly (P = 0.03). Side-effect and pain-interference scores remained essentially unchanged in this small sample of patients.

Adult↗

Baclofen pump pocket infection: a case report of successful salvage with muscle flap.

Programmable pump for continuous infusion of intrathecal baclofen, an agonist of the inhibitory neurotransmitter gamma-aminobutyric acid, is nowadays being widely used to control spasticity. The most common complications leading to explantation of the pumps are skin breakdown and infection at the pump implantation site which cannot be effectively treated without pump removal. We report a 37-year-old man who developed a baclofen pump pocket infection that did not respond to antibiotic therapy. Because the continuation of intrathecal baclofen administration was critical to the patient, and because the high cost of the pump precluded its prompt replacement, the pump was salvaged using the ipsilateral rectus abdominis muscle that was elevated on its inferior vascular pedicle and wrapped around the pump. Abdominal skin was then approximated, leaving a small portion of exposed muscle overlying the refill site that was covered by a split-thickness skin graft. Continuous intrathecal baclofen administration was never discontinued. Three months later, the pump's refill site could be easily identified manually for pump refill. There were no signs of recurrent infection during the 2-year follow-up period.

Adult↗

Intrathecal baclofen for the treatment of spasticity of cerebral origin.

Nurses monitoring children receiving intrathecal baclofen therapy can assist with management of these patients by being aware of possible complications related to a change in tone, medication withdrawal, or overdose. The tone management team relies on family care providers, school nurses, ambulatory clinic nurses, and outside physical and occupational therapists to provide information and updates on changes in patient status as needed. Close collaboration and communication regarding the child and his/her response to ITB is essential to providing safe and effective care for this challenging population of patients.

Baclofen↗